This application seeks support for the growth of a Program of research directed toward better understanding of the molecular mechanisms of cellular functions of ion transport across cell membranes. Investigations of the molecular mechanisms of ion transport seek to solve four major unsolved problems: First, the factors which determine the relative affinities of passive and active transport systems for different ions; second, the mechanisms which regulate the maximum rate of transport for each ion; third, the means by which scaler chemical bond energy is converted to vectorial work in the process of active transport; fourth, the ionic basis of the electrical properties of biological membranes. Researches on the cellular functions of ion transport include studies of the role of this process in the regulation of cell composition of volume, osmoregulation, excitation, and conduction. Experiments designed to answer questions relevant to these problems are carried out with model systems, particularly thin lipid bilayers, red cells, cardiac muscle and various marine plants and animals. The experiments involve observations under various conditions of the electrical properties, fluxes of tracer ions, immunological properties, ultrastructure as revealed by freeze-fracture electron microscopy, and chemico-physical properties as indicated by fluorescence, electron spin resonance, nuclear magnetic resonance and absorption spectroscopy of membranes. The major new projects for which support is sought in the supplemental application are: 1) The establishment of an electron probe microanalysis unit and 2) The synthesis and characterization in solution and in membranes of molecules which produce voltage dependent conductance changes in bilayers. We also request support for expansion of several existing projects in groups I and II.